PB1754: HOMOZYGOUS DELETION OF ETV6: EARLY T-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA OR PRECURSOR T-LYMPHOBLASTIC LYMPHOMA
Authors: Miguel Ángel Perera Álvarez, Juan Francisco Rodríguez López, Jorge Rodríguez-Afonso, Paula Reyes-González-Casanova, Dolly Viviana Fiallo Suarez, Maria Angelina Lemes Castellano, Maria Violeta Vidal Ballester, Ruth Stuckey, Carlos Rodriguez Medina, Cristina Bilbao, Maria Teresa Gomez Casares
Journal: HemaSphere (2023)

Topic: 2. Acute lymphoblastic leukemia - Clinical Background: Precursor T-lymphoblastic lymphoma (T-LBL), which is biologically similar to precursor T-acute lymphoblastic leukemia (T-ALL), is derived from immature lymphoid cells of T-cell lineage. The initial clinical manifestation of T-LBL usually takes the form of a mediastinal mass or lymphadenopathy, whereas T-ALL patients present with predominant manifestation of bone marrow and peripheral blood disease. Early T-cell precursor ALL/LBL (ETP-ALL/LBL) is a rare, high risk subtype of T-cell ALL/LBL (T-ALL/LBL). The differentiation between T-LBL/T-ALL and ETP-ALL is mainly by flow cytometry, although certain cases are difficult to differentiate. Aims: Here we report a case with difficult diagnosis between T-LBL/T-ALL and ETP-ALL. Methods: We report the clinical case of a patient with T-cell precursor neoplasm together with cytogenetic (Karyotype and FISH), immunophenotype and molecular analyses (Next Generation Sequencing) were carried out according to standard diagnostic procedures and molecular analyses. Results: The case is a 34-year-old male presented with a mediastinal mass and polyadenopathy. Biopsy of a lymphadenopathy showed infiltration positive for CD99, TdT+, CD7, CD56, weakly for CD3 (and negative for CD123, CD34, CD4 and CD8, TCRG, TCRB, CD1a), with an which rendered initial suspicion of T-LBL. Peripheral blood analysis at that time did not suggest aberrant cellularity. Bone marrow biopsy showed infiltration with 34% aberrant cellular by morphology. According to flow cytometry 25.3% of cells were undifferentiated aberrant cells, with intense expression for CD7, but negative for specific cell line markers (cyMPO-, cyCD3-, CD19, CD79b). Infiltrated cells expressed and positive for CD34, CD33, TDTn and CD45RA in the absence of expression of CD2, CD5, CD4 and CD8. According to genetic and cytogenetic analyzes revealed, the patient showed normal karyotype, homozygous deletion of ETV6 (12p13.2) by FISH and the following CNV losses by NGS: PTPN11 (20%), ETV6 (50%) and KRAS (20%). Altogether these results suggest possible chromothripsis of chromosome 12 accompanying the homozygous deletion of ETV6. Summary/Conclusion: According to the WHO2022 lymphoid classification, there is no genetic alteration associated with ETP-ALL, thus, the diagnosis is difficult at the present time. Combining data from bone marrow cell morphology, flow cytometry, cytogenetics and molecular biology may be of valuable help. Our case reflects the complex diagnosis of patients with ambiguous lineage precursor neoplasms. Based on the literature, both chromothripsis and ETV6 deletions have been described as ETP-ALL, in addition, ETV6 deletion has also been found in 33% of ETP-ALL compared to 10% of non-ETP-ALL. On the other hand, we have not found in the literature T-LBL cases with ETV6 deletion. In conclusion, the diagnosis of ETP-ALL is still not well defined and presents common features of T-ALL. The identification of genetic alterations that help to distinguish between T-LBL/T-ALL and ETP-ALL diagnoses is important since treatment regimes are different for each subtype. In this case, although the bone marrow morphology and the histology of the adenopathy suggest T-ALL/LL-T, flow cytometry and genetics support the diagnosis of ETP-ALL. Keywords: T cell lymphoma, Flow cytometry, Acute lymphoblastic leukemia, ETV6